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Pathogenesis of Hepatic Steatosis and Fibrosis: Role of Leptin

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Leptin

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Abstract

Nonalcoholic fatty liver disease (NAFLD) encompasses a spectrum of liver abnormalities, ranging from simple steatosis, to steatohepatitis and cirrhosis, in the absence of “excessive” alcohol consumption or any other identifiable cause(s) for liver disease [1]. Histologically, NAFLD can be categorized into: (1) simple steatosis in the absence of hepatocellular injury (nonalcoholic fatty liver, NAFL); and (2) steatohepatitis (nonalcoholic steatohepatitis, NASH), characterized by the presence of steatosis and inflammation with hepatic injury (ballooning), with or without fibrosis [1]. NASH can progress to cirrhosis, liver failure, and rarely liver cancer, whereas the progression to more severe forms of liver disease is minimal in patients with NAFL. Steatosis is the hallmark of NAFL and NAFLD and can be defined chemically, when intrahepatic triglyceride (IHTG) content exceeds 5 % of liver volume or liver weight [2], histologically, when 5 % of hepatocytes contain visible intracellular triglyceride [3], and radiologically, by using magnetic resonance spectroscopy (MRS) [4]. The results from one study in subjects who were considered to be at low-risk for NAFLD (i.e., normal weight, normal fasting serum glucose and alanine aminotransferase concentrations, and absence of diabetes) indicate an upper “normal” amount of IHTG of 5.6 % of liver volume, which represented the 95th percentile in this population [5]. Data from another study found the 95th percentile for IHTG content was 3 % in young lean subjects with normal oral glucose tolerance [6].

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Authors and Affiliations

  1. Center for Human Nutrition and Atkins Center of Excellence in Obesity Medicine, Washington University School of Medicine, St. Louis, MO, USA

    Faidon Magkos Ph.D. & Elisa Fabbrini M.D., Ph.D.

  2. Center for Human Nutrition, Washington University School of Medicine, 660 South Euclid Avenue, Campus, 8031, St. Louis, MO, 63110, USA

    Samuel Klein M.D.

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  1. Faidon Magkos Ph.D.
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  2. Elisa Fabbrini M.D., Ph.D.
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  3. Samuel Klein M.D.
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  1. Division of Endocrinology, Diabetes and Metabolism, University of Tennessee Health Science Center, Memphis, Tennessee, USA

    Sam Dagogo-Jack, MD

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Magkos, F., Fabbrini, E., Klein, S. (2015). Pathogenesis of Hepatic Steatosis and Fibrosis: Role of Leptin. In: Dagogo-Jack, MD, S. (eds) Leptin. Springer, Cham. https://doi.org/10.1007/978-3-319-09915-6_8

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